Project 4, led by Drs. Lynn Matrisian and Wellington Pham, focuses on developing optical beacons and MRI contrast agents for the in vivo detection of tumor-associated metalloproteinase activity as a novel mechanism to monitor response to tumor therapy. Members of the matrix metalloproteinase (MMP) family are implicated in the matrix degradation associated with cancer invasion. There is substantial literature indicating the involvement of specific MMP family members in specific cellular processes related to cancer, including the activation of growth factors, angiogenesis, infiltration of inflammatory cells, and invasion. These investigators propose to take advantage of this knowledge to devise a series of non-invasive in vivo imaging reagents that will probe the proteolytic status of a tumor to aid in treatment decisions, and rapidly assess the response to standard and targeted cancer chemotherapies. Dr. Pham, a chemist by training, brings extensive experience with the design and synthesis of optical probes for proteolytic activity, and Dr. Matrisian, a cancer biologist, has extensive experience exploring the role of metalloproteinases in mouse models of cancer. Murine models of benign, malignant, and metastatic colorectal cancer will be used in this project, and the response to cancer therapies directed at the epidermal growth factor (EGF) receptor axis will be tested in collaboration with projects 1 and 3 of this ICMIC proposal.